Ocular Lens

ABSTRACT

An ocular lens has a refractive optics structure formed from a polyisobutylene-based material and a glassy segment that is non-reactive to ocular fluid and that maintains in vivo transparency for a substantial time period. The material has a central elastomeric polyolefinic block and thermoplastic end blocks (such as a triblock polymer backbone comprising polystyrene-polyisobutylene-polystyrene). The material is preferably flexible such that the refractive optics structure can be folded upon itself and introduced through a small scleral incision. The lens device includes an optic portion and preferably either an annular haptic element or one or more haptic elements adapted to rest within a capsular bag formed by a surgical procedure. A portion of the lens device may be loaded with at least one therapeutic agent that interferes with proliferation of the epithelial cells of the eye to protect against PCO.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. Ser. No. 11/004,538,filed Dec. 3, 2004, which claims priority from U.S. Provisional PatentApplication 60/526,965, filed Dec. 5, 2003 and U.S. Provisional PatentApplication 60/526,966, filed Dec. 5, 2003, all herein incorporated byreference in their entirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates broadly to ocular lens devices. Moreparticularly, this invention relates to intraocular lens devices thatare surgically implanted within the capsular bag of a human eye.

2. State of the Art

The human eye has an anterior chamber between the cornea and the iris, aposterior chamber behind the iris containing a crystalline lens, avitreous chamber behind the lens containing vitreous humor, and a retinaat the rear of the vitreous chamber. The crystalline lens of a normalhuman eye has a lens matrix in addition to a lens capsule attached aboutits periphery to the ciliary muscle of the eye by zonules. This lenscapsule has elastic optically clear anterior and posterior membrane-likewalls, which are commonly referred by ophthalmologists as anterior andposterior capsules, respectively. Between the iris and ciliary muscle isan annular space called the ciliary sulcus.

The human eye possesses natural accommodation capability. Naturalaccommodation involves relaxation and constriction of the ciliary muscleby the brain to provide the eye with near and distant vision. Thisciliary muscle action is automatic and shapes the natural crystallinelens to the appropriate optical configuration for focusing the lightrays entering the eye onto the retina.

The human eye is subject to a variety of disorders which degrade, ortotally destroy, the ability of the eye to function properly. One of themore common of these disorders involves progressive clouding of thecrystalline lens matrix resulting in the formation of what is referredto as a cataract.

It is common practice to cure a cataract by surgically removing theclouded crystalline lens and implanting an artificial intraocular lensin the eye to replace the natural lens. The prior art is replete with avast assortment of intraocular lenses. Examples of such lenses aredescribed in the following patents: U.S. Pat. Nos. 4,254,509, 4,298,996,4,842,601, 4,963,148, 4,994,082, and 5,047,051. As is evident from theabove patents, intraocular lenses differ widely in their physicalappearance and arrangement.

Typically, cataracts are surgically removed by anterior capsulotomy,which involves forming an incision in the sclera beneath the cornea.Tooling is inserted through this incision and manipulated to open theanterior capsule of the natural lens while leaving intact a capsularbag. This capsular bag has an elastic posterior capsule, an anteriorcapsular remnant or rim about the anterior capsule opening and acapsular bag sulcus. The capsular bag sulcus is located between theanterior capsule remnant and the outer circumference of the posteriorcapsule. The capsular bag remains attached about its periphery to thesurrounding ciliary muscle of the eye by the zonules of the eye. Thelens matrix is extracted from the capsular bag through the scleralincision by phacoemulsification and aspiration (or in some other way).An intraocular lens is then implanted through the scleral incision suchthat it lies within the capsular bag.

A relatively recent and improved form of anterior capsulotomy known ascapsulorhexis forms a generally circular-shaped opening through theanterior capsule by tearing the anterior capsule of the natural lenscapsule along a generally circular tear line substantially coaxial withthe lens axis and removing the generally circular portion of theanterior capsule surrounded by the tear line. If performed properly,capsulorhexis provides a generally circular opening through the anteriorcapsule of the natural lens capsule substantially coaxial with the axisof the eye and surrounded circumferentially by a continuous annularremnant or rim of the anterior capsule having a relatively smooth andcontinuous inner edge bounding the opening.

Another anterior capsulotomy procedure, referred to as an envelopecapsulotomy, forms a generally arch-shaped opening through the anteriorcapsule by cutting a horizontal incision in the anterior capsule, thencutting two vertical incisions in the anterior capsule intersecting andrising from the horizontal incision, and finally tearing the anteriorcapsule along a tear line having an upper upwardly arching portion whichstarts at the upper extremity of the vertical incision and continues ina downward vertical portion parallel to the vertical incision whichextends downwardly and then across the second vertical incision. Thisprocedure produces a generally arch-shaped anterior capsule openingcentered on the axis of the eye. The opening is bounded at its bottom bythe horizontal incision, at one vertical side by the vertical incision,at its opposite vertical side by the second vertical incision of theanterior capsule, and at its upper side by the upper arching portion ofthe capsule tear.

Another capsulotomy procedure, typically referred to as can openercapsulotomy, forms a generally circular-shaped opening through theanterior capsule by piercing the anterior capsule at a number ofpositions along a circular line substantially coaxial with the axis ofthe eye and then removing the generally circular portion of the anteriorcapsule circumferentially surrounded by the line. This procedureproduces a generally circular anterior capsule opening substantiallycoaxial with the axis of the eye and bounded circumferentially by anannular remnant or rim of the anterior capsule.

Intraocular lenses differ widely in their physical appearance andarrangement, yet generally have a central optical region (or optic) andhaptics which extend outward from the optic and engage the interior ofthe eye in such a way as to support the optic in a position centered onthe axis of the eye. Intraocular lenses also differ with respect totheir accommodation capability, and their placement in the eye.Accommodation is the ability of an intraocular lens to accommodate, thatis to focus the eye for near and distant vision. Most non-accommodatinglenses have single focus optics, which focus the eye at a certain fixeddistance only and require the wearing of eyeglasses to change the focus.Other non-accommodating lenses have bifocal optics which image both nearand distant objects on the retina of the eye. The brain selects theappropriate image and suppresses the other image, so that a bifocalintraocular lens provides both near vision and distant vision sightwithout eyeglasses. Bifocal intraocular lenses, however, suffer from thedisadvantage that 20% of the available light is lost in scatter, therebyproviding lessened visual acuity. Newer intraocular lenses, such as theintraocular lens described in U.S. Pat. No. 6,685,741, achievemultifocal accommodation in response to compressive forces exerted onthe haptics of the lens. Such compressive forces are derived fromnatural brain-induced contraction and relaxation of the ciliary muscleand increases and decreases in vitreous pressure. Such accommodatingintraocular lenses are surgically implanted within the evacuatedcapsular bag of the patient's eye through the scleral incision andanterior capsule opening in the capsular bag. The haptics of the lensare situated within the outer perimeter of the capsular bag and aredesigned to support the optics along the optical axis of the eye in amanner that minimizes stretching of the capsular bag.

After surgical implantation of the intraocular lens in the capsular bagof the eye, active endodermal cells on the posterior side of theanterior capsule rim of the capsular bag causes fusion of the rim to theelastic posterior capsule wall by fibrosis. This fibrosis occurs aboutthe haptics of the IOL in such a way that the haptics are effectively“shrink-wrapped” by the fibrous tissue in such a way as to form radialpockets in the fibrous tissue. These pockets contain the haptics withtheir outer ends positioned within the outer perimeter of the capsularbag. The lens is thereby fixated with the capsular bag with the lensoptic aligned with the optical axis of the eye. The anterior capsule rimshrinks during fibrosis, and this shrinkage combined with theshrink-wrapping of the haptics causes some radial compression of thelens in a manner which tends to move the lens optic along the opticalaxis of the eye. The fibrosed, leather-like anterior capsule rimprevents anterior movement of the optic and urges the optic rearwardlyduring fibrosis. Accordingly, fibrosis induced movement of the opticoccurs posteriorly to a distant vision position in which either (orboth) the optic and inner ends of the haptics press rearwardly againstthe elastic posterior capsule wall, thereby stretching the posteriorcapsule wall rearwardly.

With time, depending on the rearward pressure of the intraocular lens onthe posterior capsule wall as well as other factors (such as lensmaterial, lens geometry, angulation, sharpness, wrinkles in theposterior capsule wall, etc), epithelium cells can migrate between theposterior capsule wall and the lens and reside and multiply in thesespaces. Excessive build up of the cells in this area can lead toopacification of the optic. This opacification, commonly referred to asposterior capsule opacification (PCO), causes clouding of vision and canlead to blurring and possibly total vision loss. The process of PCO isslow and clinical changes often take one to two years to becomeapparent. PCO is typically treated by YAG laser capsulotomy. However, interms of health economics, PCO is very expensive to treat.

Special care must also be taken that the material of the lens opticmaintains transparency after it has been implanted within the eye andsubject to ocular fluids. This characteristic is referred to herein as“in vivo transparency” or “in vivo transparent”. Any significantclouding of the lens optic due to its interaction with ocular fluids canlead to blurring and possibly total vision loss in a manner similar toPCO. In U.S. Pat. No. 6,102,939, the inventor describes the crackresistance and biostability of a prosthesis implanted in vivo whereinthe prosthesis formed from a polyolefinic copolymer material having atriblock polymer backbone comprisingpolystyrene-polyisobutylene-polystyrene, which is herein referred to as“SIBS”, while also mentioning the desirability of long term elastomersfor use in intraocular lenses as well as a long list of otherapplications (e.g., vascular grafts, endoluminal grafts, finger joints,indwelling catheters, pacemaker lead insulators, breast implants, hearvalves, etc.). However, this patent fails to address importantconsiderations (such as in vivo transparency) with regard to thesuitability of the SIBS material for use in the ocular environment.

Modern intraocular lenses are made flexible where they can be folded inhalf to enable placement in the capsular bag through the scleralincision. However, such lenses typically have relatively lower indicesof refraction, and thus such intraocular lenses are required to bethicker to provide the desired magnification characteristics of theintraocular lens. More particularly, the prior art foldable intraocularlenses are typically made of a silicone-based polymer with an index ofrefraction of 1.3 to 1.4, or made from an acrylic material with an indexof refraction of 1.46. Such refractive indices are relatively low (forexample, PMMA which is typically used for a rigid IOL has a refractiveindex of 1.49). Thus, such intraocular lenses are required to be thickerto provide the desired magnification characteristics of the intraocularlens. One skilled in the art understands that the magnification of alens is dependent upon three values: i) radii of curvature; ii) index ofrefraction; and iii) thickness of the lens. Thus, for any given lensthickness, a greater index of refraction provides a greater degree ofmagnification. Alternatively, for any desired magnification, the higherthe index of refraction enables the lens to be thinner. The thinner thelens, the smaller it can be folded or rolled. This allows the scleralincision to be made smaller and possibly avoids the use of sutures inclosing the scleral incision. Suturing the scleral incision isdisadvantageous because the scleral incision site, if not suturedproperly, becomes a site of infection and leakage of aqueous fluid.Moreover, if the sutures are too lose or tight, astigmatism can form dueto distortion of the cornea. On the other hand, if the scleral incisionis small (e.g., less than a 2 mm slit), the incision will close on itsown without the use of sutures. In addition, the thinner the lens, themore its radius of curvature can be deformed and/or axial displaced bychanging tension in the anterior capsule by muscular contraction,thereby providing for enhanced accommodation after implantation.

Modern intraocular lens also act as a spectral filters that block outultra-violet (UV) light that may burn the retina. Such UV light blockingcapability is typically provided by additives that absorb UV radiation.Such additives are generally molecules that contain aromatic groups.These additives can migrate out of the polymeric material of the lensand cause toxic reactions.

Thus, there remains a need in the art to provide an intraocular lensdevice that is realized from a flexible biocompatible material thatmaintains in vivo transparency and has a relatively high index ofrefraction. Such features provide for a foldable intraocular lens thatrequires a small incision in the sclera, and thus provides for moreeffective healing of the eye as noted above. The relatively high indexof refraction also provides for an intraocular lens with improvedmagnification capabilities.

There is also a need in the art to provide an intraocular lens devicethat is realized from a biocompatible material with ultra-violet lightblocking capability that does not risk toxic reaction in the eye.

There is also need in the art to provide an intraocular lens device thatinhibits epithelium cell migration and multiplication to thereby protectagainst PCO.

Several methods of manufacturing flexible, biocompatible intraocularlens devices are known, such as injection molding, spin casting,compression molding and transfer molding. These methods typically employa polished stainless steel mold cavity that is formed in a geometry thatachieves the desired curvature. Several significant problems have beenassociated with these molding techniques. One problem is that thestainless steel mold requires cleaning between molding cycles, whichincreases the labor costs and production costs associated with thefinished product. Another problem is that steel molds typically havesmall gaps between the mold halves that allow “flash” to form in thegaps during the molding operation. Flash is unwanted material attachedto the mold parting line on the finished product. This flash materialmust be removed from the finished product, which again increases thelabor costs and production costs associated with the finished product.

Thus, there remains a need in the art to provide improved techniques forthe manufacture of flexible, biocompatible intraocular lens deviceswhich are less expensive than the prior art manufacturing techniques.

SUMMARY OF THE INVENTION

It is therefore an object of the invention to provide an ocular lensdevice that is realized from a flexible biocompatible material thatmaintains in vivo transparency and has a relatively high index ofrefraction.

It is another object of the present invention to provide such an ocularlens device that is suitable as an intraocular implant that requires asmall incision in the sclera of the eye, and thus provide for moreeffective healing of the eye post-operatively as noted above.

It is a further object of the present invention to provide an ocularlens device that provides improved magnification capabilities.

It is yet another object of the present invention to provide an ocularlens device that is realized from a biocompatible material withultra-violet light blocking capability that does not risk toxic reactionin the eye.

It is another object of the present invention to provide an intraocularlens device that inhibits epithelium cell migration and multiplicationto thereby protect against PCO.

It is a further object of the present invention to provide a method (andcorresponding apparatus) for the manufacture of the improved intraocularlens devices described herein.

It is yet another object of the present invention to provide a method(and corresponding apparatus) for the manufacture of intraocular lensdevices which is less expensive than the prior art manufacturingtechniques.

In accord with these objects, which will be discussed in detail below,an ocular lens device includes a refractive optics structure formed froma polyisobutylene-based material and a glassy segment. Preferably, thematerial has a central elastomeric polyolefinic block and thermoplasticend blocks (such as a triblock polymer backbone comprisingpolystyrene-polyisobutylene-polystyrene). The material of the refractiveoptics structure maintains in vivo transparency during implantation inits intended ocular environment for a substantial period of time. Thematerial of the lens device is flexible such that it can be folded orrolled upon itself, which allows for the scleral incision to be madesmall (e.g., less than a 2 mm slit) and thus enables more effectivehealing of the scleral incision without sutures. The lens devicepreferably includes an optic portion and at least one haptic elementthat are adapted to rest within a capsular bag formed by a surgicalprocedure. The at least one haptic element supports the optic portionwithin the capsular bag. Preferably, the material of the refractiveoptics structure inherently blocks ultra-violet light without theaddition of any additives.

According to one embodiment of the invention, the lens device may have aplurality of haptic elements that project radially away from the opticportion.

According to another embodiment of the invention, the lens device mayhave an annular haptic element that extends radially outward from theoptic portion. The annular haptic element projects radially outward fromthe optic portion at an angle relative to the plane of the optic regionat an angle between 0 and 45 degrees, and preferably at an angle between10 and 20 degrees, and most preferably at an angle of 15 degrees. Theoptic portion preferably has a front convex surface and a flat backsurface in addition to a stepped wall structure at its periphery.

According to yet another embodiment of the invention, the material ofthe lens device may be loaded with therapeutic drugs that interfere withcell proliferation, which is advantageous in intraocular applications inorder to protect against PCO.

According to another embodiment of the invention, the in vivotransparent nature of the material of the refractive optics structure isaccomplished by washing the polyisobutylene-based polymer tosubstantially remove remnant salts, and processing thepolyisobutylene-based polymer at a controlled temperature(s) and/or acontrolled processing time(s) to form a refractive optics structure. Inone methodology, the refractive optics structure is formed by processingthe polyisobutylene-based polymer material at controlled temperaturesthat are significantly less that the melting point of thepolyisobutylene-based polymer. In another methodology, the refractiveoptics structure is formed by rapidly heating the polyisobutylene-basedpolymer to a temperature at or near its melting point, utilizing theresultant polymer melt to form the refractive optics structure in aclosed mold, and then rapidly cooling the polymer/mold back to roomtemperature.

According to yet another embodiment of the invention, the lens devicechanges its radius of curvature or position in response to changes intension of the lens capsule and/or from changes in pressure in thevitreous.

Additional objects and advantages of the invention will become apparentto those skilled in the art upon reference to the detailed descriptiontaken in conjunction with the provided figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration showing anatomic details of the human eye inaddition to the implantation of an intraocular lens device in accordancewith the present invention.

FIG. 2 is a front view of an exemplary embodiment of an intraocular lensdevice in accordance with the present invention.

FIGS. 3 and 4 illustrate the operation of the intraocular lens device ofFIG. 2 to provide for accommodation of the eye in response tocontraction and relaxation of the ciliary muscles of the eye.

FIG. 5 is a front view of an alternate embodiment of an intraocular lensdevice in accordance with the present invention.

FIGS. 6A, 6B and 6C illustrate different annular haptic designs that canbe utilized in the embodiment of FIG. 5.

FIGS. 7 and 8 are front views of alternate embodiments of an intraocularlens device in accordance with the present invention.

FIGS. 9A and 9B illustrate the operation of an alternate embodiment ofintraocular lens device in accordance with the present invention inproviding for accommodation of the eye in response to contraction andrelaxation of the ciliary muscles of the eye.

FIG. 10 is a cross-sectional schematic view of a centrifugal castingapparatus for use in fabricating an ocular lens device in accordancewith the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Turning now FIG. 1, there is shown a human eye 10 from which the naturalcrystalline lens matrix was previously removed by a surgical procedureinvolving an anterior capsulotomy, in this case a continuous tearcircular tear capsulotomy, or capsulorhexis. The natural lens comprisesa lens capsule having elastic anterior and posterior walls, which arereferred herein as anterior and posterior capsules, respectively. Asmentioned earlier, continuous tear circular capsulotomy, orcapsulorhexis, involves making an incision in the sclera of the eye.Tooling is inserted through this incision and manipulated to tear theanterior capsule along a generally circular tear line in such a way asto form a relatively smooth-edged circular opening in the center of theanterior capsule. The cataract is removed from the natural lens capsulethrough the scleral incision. After completion of this surgicalprocedure, the eye includes an optically clear anterior cornea 12, anopaque sclera 14, a retina 16, an iris 18, a capsular bag 20 behind theiris, and a vitreous cavity 21 behind the capsular bag filled with thegel-like vitreous humor. The capsular bag 20 is the structure of thenatural lens of the eye which remains intact after the capsulorhexis hasbeen performed and the natural lens matrix has been removed. Thecapsular bag 20 includes an annular anterior capsular remnant or rim 22and an elastic posterior capsule 24 which are joined along the perimeterof the bag 20 to form an annular crevice-like bag structure between thecapsular rim 22 and posterior capsule 24. The capsular rim 22 is theremnant of the anterior capsule of the natural lens which remains aftercapsulorhexis has been performed on the natural lens. This rimcircumferentially surrounds a central, generally round anterior opening26 (capsulotomy) in the capsular bag through which the natural lensmatrix was previously removed from the natural lens. The capsular bag 20is secured about its perimeter to the ciliary muscle of the eye byzonules 30. Eye 10 also includes an optical axis OA-OA that is animaginary line that passes through the optical center of intraocularlens 32. An optical axis OA in the human eye 10 is generallyperpendicular to a portion of cornea, natural lens and retina.

Natural accommodation in a normal human eye involves contraction andrelaxation of the ciliary muscle of the eye by the brain in response tolooking at objects at different distances. Ciliary muscle relaxation,which is the normal state of the muscle, positions and shapes the humancrystalline lens for distant vision. Ciliary muscle contractionpositions and shapes the human crystalline lens for near vision. Thebrain-induced change from distant vision to near vision is referred toas accommodation.

An accommodating intraocular lens 32 according to the present inventionis implanted through the scleral incision into the capsular bag 20 ofthe eye 10. The intraocular lens 32 replaces and performs theaccommodation function of the removed natural crystalline lens. Asillustrated in FIG. 2, the intraocular lens 32 of the present inventionincludes an optic portion 34 with an outer peripheral edge 36. Threehaptic elements 40A, 40B, 40C (collectively, 40) project radiallyoutward from the peripheral edge 36 of optic portion 34. The hapticelements 40A, 40B, 40C are preferably integrally formed with andpermanently connected to the outer peripheral edge 36 of optic portion34. The haptic elements 40A, 40B, 40C include respective end portions42A, 42B, 42C that are adapted to rest in and engage the annularcapsular bag 20, which is disposed between the capsular rim 22 andposterior capsule 24. The end portions 42A, 42B, 42C are held in placethrough compressive forces exerted by the inner surfaces of the capsularbag 20 thereon. In this position, the optic portion 34 is substantiallyaligned with the optical axis OA of the eye, the posterior side of theoptical portion 34 faces the elastic posterior capsule 24, and the endportions 42A, 42B, 42C fit snuggly within the capsular bag 20 at theradially outer perimeter of the bag, which prevents decentration of theintraocular lens 32.

The haptic elements 40A, 40B, 40C also include hinge portions 44A, 44B,44C which join the end portions of the haptic elements to the opticportion 34. The haptic elements 40A, 40B, 40C are flexible about therespective hinge portions 44A, 44B, and 44C anteriorly and posteriorlyrelative to the optic portion 34. The hinge portions 44A, 44B, 44C maybe formed by narrowing structures as shown. Alternatively, the hingedportions may be formed by grooves or other structural features of thehaptic elements 40A, 40B, and 40C. In this manner, the haptic elements40A, 40B, 40C are adapted to flex about respective axes 46A, 46B, 46Csuch that the optic portion 34 moves generally along the optical axis OAof eye 10, thereby achieving axial displacement of the optic portion 34in a direction along optical axis OA. By designing such flexioncharacteristic into the haptic elements 40A, 40B, 40C, the intraocularlens 32 allows an eye to achieve multifocal visual imaging without theaid of eyeglasses.

In alternate embodiments, the haptic elements 40 are adapted to transmitradial forces applied to rim of capsular bag by ciliary musclecontraction and relaxation to the optic portion 34, whose radius ofcurvature (e.g., diopter) changes in response thereto. In suchembodiments, the haptic elements 40 are preferably adapted such that theoptic portion 34 is not substantially displaced along the optical axisOA of eye 10 in response to such ciliary muscle contraction andrelation. By designing such deformation characteristics into the hapticelements 40 and the optic portion 34, the intraocular lens 32 allows theeye to achieve multifocal visual imaging without the aid of eyeglasses.

According to the preferred embodiment of the present invention, theintraocular lens 32 (or a portion of the lens 32 such as the opticportion 34) is formed from a polyolefinic copolymer material having atriblock polymer backbone comprisingpolystyrene-polyisobutylene-polystyrene, which is herein referred to as“SIBS”. Non-cross linked high molecular weight polyisobutylene (PIB) isa soft putty-like material with a Shore hardness less than 20 A. Whencopolymerized with polystyrene, it can be made at hardnesses ranging upto the hardness of polystyrene, which has a Shore hardness of 100 D.Thus, depending on the relative amounts of styrene and isobutylene, theSIBS material can have a range of hardnesses from as soft as Shore 10 Ato as hard as Shore 100 D. In this manner, the SIBS material can beadapted to have the desired elastomeric and hardness qualities. In thepreferred embodiment, the SIBS material for lens 32 (including the opticportion 34 and the haptic elements) is flexible such that it can befolded and/or rolled upon itself, which minimizes the size of thescleral incision required for implantation and enables healing of thescleral incision without sutures. It therefore provides for moreeffective healing of the eye post-operatively as noted above. Afterinserting the lens 32 in its folded state through the scleral incision,the lens 32 is unfolded and positioned such that it is supported withinthe capsulary bag. The optic portion 34 and the haptic elements can berealized from the same SIBS material, a different SIBS material (e.g., aSIBS material with a different hardness quality), or from differentbiocompatible polymers altogether. When formed from different materials,the haptic elements can be insert-molded, adhered with an adhesive orheat or sonic welded to the optics portion 34 of the lens 32. Details ofthe SIBS material is set forth in U.S. Pat. Nos. 5,741,331; 6,102,939;6,197,240; 6,545,097, which are hereby incorporated by reference intheir entirety.

The SIBS material of the intraocular lens 32 may be polymerized undercontrol means using carbocationic polymerization techniques such asthose described in U.S. Pat. Nos. 4,276,394; 4,316,973; 4,342,849;4,910,321; 4,929,683; 4,946,899; 5,066,730; 5,122,572; and Re 34,640,each herein incorporated by reference in its entirety. The amount ofstyrene in the copolymer material is preferably between about 1 molepercent to 30 mole %. The styrene and isobutylene copolymer materialsare preferably copolymerized in solvents.

In accord with another aspect of the invention, it is expected thatalternative polymeric materials are suitable for the practice of thepresent invention. Such alternative polymeric materials preferablyinclude polyisobutylene-based material capped with a glassy segment. Theglassy segment provides hard domains for the elastomeric polyisobutyleneand is non-reactive in the ocular environment (e.g., it will not reactwith the fluid of the eye). The glassy segment preferably does notcontain any cleavable group which will release in the presence of bodyfluid inside the human eye and cause toxic side effects. Moreover, thepolyisobutylene-based material and glassy segment preferably avoid cellencapsulation in the ocular environment. The glassy segment can be avinyl aromatic polymer (such as polystyrene, α-methylstyrene, or amixture thereof), or a methacrylate polymer (such as methylmethacrylate,ethylmethacrylate, hydroxymethalcrylate, or a mixture thereof). Suchmaterials preferably have a general block structure with a centralelastomeric polyolefinic block and thermoplastic end blocks. Even morepreferably, such materials have a general structure:

-   -   BAB or ABA (linear triblock),    -   B(AB)n or A(BA)n (linear alternating block), or    -   X-(AB)n or X-(BA)n (includes diblock, triblock and other radial        block copolymers),    -   where A is an elastomeric polyolefinic block, B is a        thermoplastic block, n is a positive whole number and X is a        starting seed molecule.        Such materials may be star-shaped block copolymers (where n=3 or        more) or multi-dendrite-shaped block copolymers.

During a post-operative healing period on the order of two to threeweeks following surgical implantation of the lens 32 in the capsular bag20, epithelial cells cause fusion of the inner surface of the rim 22 tothe posterior capsule 24 by fibrosis. In the case that the hapticelements 40A, 40B, 40C are formed from a material that avoids cellencapsulation in the ocular environment, the non-encapsulating nature ofthe material causes the fibrosis to occur around the haptic elements40A, 40B, 40C in such a way that the haptic elements are loosely wrappedby the capsular bag 20 to form pockets in the fibrosed material. Thesepockets cooperate with the haptic elements 40A, 40B, 40C to position andcenter the lens 32 in the eye. Ciliary muscle induced flexing of thelens 32 during fibrosis can be resisted or prevented by using acyclopegic and/or by wrapping sutures around the hinge portions 44A,44B, 44C. Removal of these sutures after completion of fibrosis may beaccomplished by using sutures that are either absorbable in the fluidwithin the eye or by using sutures made of a material, such as nylon,which can be removed by a laser.

Natural accommodation in a normal human eye involves shaping of thenatural crystalline lens by automatic contraction and relaxation of theciliary muscle of the eye by the brain to focus the eye at differentdistances. Ciliary muscle relaxation shapes the natural lens for distantvision. Ciliary muscle contraction shapes the natural lens for nearvision. The accommodating intraocular lens 32 is adapted to utilize thissame ciliary muscle action, the fibrosed capsular rim 22, the elasticposterior capsule 24, and the vitreous pressure within the vitreouscavity 21 to effect accommodation movement of the lens optic 34 alongthe optic axis of the eye between its distant vision position of FIG. 3to its near vision position of FIG. 4. Thus, when looking at a distantscene, the brain relaxes the ciliary muscles. Relaxation of the ciliarymuscles stretches the capsular bag 20 to its maximum diameter and itsfibrosed anterior rim 22 to the taut trampoline-like condition orposition discussed above. The taut rim deflects the optics portion 34rearwardly to its posterior distant vision position of FIG. 3 in whichthe elastic posterior capsule 24 is stretched rearwardly by the opticsportion 34 and thereby exerts a forward biasing force on the lens 32.When looking at a near scene, such as a book when reading, the brainconstricts or contracts the ciliary muscle. This ciliary musclecontraction increases the vitreous cavity pressure and relaxes thecapsular bag 20 and particularly its fibrosed capsular rim 22. Therelaxed capsular bag 20 exerts opposing endwise compression forces onthe ends of the haptic elements 40A, 40B, and 40C with resultant endwisecompression of the lens 32. Such relaxation of the capsular rim permitsthe rim to flex forwardly and thereby enables the combined forward biasforce exerted on the lens by the rearwardly stretched posterior capsuleand the increased vitreous cavity pressure to push the lens forwardly toits near vision position of FIG. 4. Intermediate vision positionsbetween the far vision position of FIG. 3 and the near vision positionof FIG. 4 are obtained by relaxation and/or contraction of the ciliarymuscles in a manner similar to that described above, which allows theeye to focus at different distances.

In alternate embodiments, such as those described below with respect toFIGS. 9A and 9B, accommodation is provided by changing the radius ofcurvature of the optic portion of the lens without substantiallychanging the position of the lens device along the optical axis (OA) ofthe eye. In these embodiments, relaxation of the ciliary muscles (whichis accomplished by the brain when looking at a distant scene) stretchesthe capsular bag 20 and its fibrosed anterior rim 22 to the tauttrampoline-like condition or position discussed above. The taut rimapplies radial tension to the haptic elements 40 and optics portion 34of the lens device 32, which causes the radius of curvature of the opticportion 34 to increase (FIG. 9A). When looking at a near scene, thebrain constricts or contracts the ciliary muscle. This ciliary musclecontraction increases the vitreous cavity pressure and relaxes thecapsular bag 20 and particularly its fibrosed capsular rim 22. Therelaxed capsular bag 20 releases the radial forces on the hapticelements 40 and the optic portion 34 of the lens device 32 such that theradius of curvature of the optic portion 34 decreases (FIG. 9B). Theseoperations provide for accommodation which allows the eye to focus atdifferent distances.

The IOL of the present invention can also be realized by differenthaptic designs, such as those that utilize two haptics, four haptics,and ring haptics as is well known in the art. FIG. 5 illustrates a topview of an IOL 32′ with an optic portion 34′ and an annular hapticelement 40′. Cross-sections for different embodiments are shown in FIGS.6A-6C. The front and back surfaces of optic portion 34′ can be of anydiopter (curvature) necessary to provide the desired correction for thepatient. For example, the front surface of the optic portion 34′ may beconvex as shown in FIGS. 6A-C or possibly concave (not shown). The backsurface of the optic portion 34′ is preferably flat as shown in FIGS.6A-6C, but it may be concave or convex to add or subtract magnification.

As shown in FIGS. 6A-6C, the angle θ of the annulus of the hapticelement 40′ relative to the plane of the optic portion 34′ (which isdisposed substantially perpendicular to the optical axis of the eye) isbetween 0 and 45 degrees, and more preferably between 10 and 20 degrees,and most preferably 15 degrees. The IOL 34′ is formed from a flexiblematerial, such as the SIBS material described above, such that it can befolded and/or rolled upon itself, which minimizes the size of thescleral incision required for implantation and enables healing of thescleral incision without sutures. It therefore provides for moreeffective healing of the eye post-operatively as noted above. Afterinserting the IOL 34′ in its folded state through the scleral incision,the IOL 34′ is unfolded and positioned such that it is supported withinthe capsulary bag. When placed in the capsular bag, the annular hapticelement 40′ is adapted to rest in and engage the annular capsular bag20, which is disposed between the capsular rim 22 and posterior capsule24. The peripheral portion 42′ of the annular haptic element 40′ is heldin place through compressive forces exerted by the inner surfaces of thecapsular bag 20 thereon. In this position, the optic portion 34′ issubstantially aligned with the optical axis OA of the eye, the posteriorside of the optical portion 34′ faces the elastic posterior capsule 24,and the peripheral portion 42′ of the annular haptic element 40′ fitssnuggly within the capsular bag 20 at the radially outer perimeter ofthe bag, which prevents decentration of the intraocular lens 32′. Thisconfiguration is similar to the configuration shown in FIG. 1.

As shown in FIGS. 6A and 6B, the outer edge of the optic portion 34′ maybe defined by a step 60, which serves as a boundary wall to preventcells from migrating from the periphery of the lens 32′ and over thearea of the optic portion 34′. Note however that the step 60 may beomitted as shown in the embodiment of FIG. 6C, especially ifantiproliferating or antimigration agents are used to prevent cellmultiplication and migration under the lens.

The embodiment of FIG. 6B is similar to the embodiment of FIG. 6A,except that the thickness (i.e., the distance between front and backsurfaces) of the optic portion 34′ is smaller in the embodiment of FIG.6B, which should allow the optic portion 34′ to be folded or rolledsmaller. In addition, the flat surface of the lens can be curved toprovide more magnification if desired. Alternate embodiments withannular haptic designs are shown in FIGS. 7 and 8.

In the embodiment of FIG. 7, a plurality of holes 44 are formed aboutthe annular haptic 40″. These holes preferably enable fluid orviscoelastic (if used) migration between the front and back of the lens32″ as well as aid in fixation of the lens to the annular capsular bagby cellular ingrowth. More particularly, during a post-operative healingperiod on the order of two to three weeks following surgicalimplantation of the lens 32″ in the capsular bag 20, epithelial cellscause fusion of the inner surface of the rim 22 to the posterior capsule24 by fibrosis. In the case that the annular haptic element 40″ isformed from the SIBS material, the non-encapsulating nature of the SIBSmaterial causes the fibrosis to occur through the holes 44 in such a waythat the haptic element 40″ is wrapped tightly by the capsular bag.Ciliary muscle induced flexing of the lens 32″ during fibrosis can beresisted or prevented by using a cyclopegic and/or by other means.

In the embodiment of FIG. 8, the annular haptic element 40′″ has aplurality of radial cuts 46 formed therein. The radial cuts 46 extendradially from the central optic portion 34′″ to the periphery of theannular haptic element 40′″ as shown. The radial cuts 46 better enableproper placement into the capsular bag.

In the embodiments of FIGS. 5-8, the circular nature of the hapticannulus helps force the lens against the posterior capsule 24 and helpsprevent wrinkles from forming in the capsule and channels for cellmigration (which can lead to PCO). In addition, the force of the annularhaptic element against the lens capsule is such that ciliary musclecontraction and relaxation causes movement of the optic region along theoptical axis by puckering of the lens (in other words, changing theangle θ). In this manner, the annular haptic provides for accommodationbetween a far vision position and near vision position in a mannersimilar to that described above with respect to FIGS. 3 and 4, and thusallows the eye to focus at different distances without the need forreading glasses. Alternatively, the annular haptic element can beadapted such that ciliary muscle contraction and relaxation causes theoptic portion of the lens to bow and change its radius of curvature asshown in FIGS. 9A and 9B.

In another embodiment shown in FIGS. 9A and 9B, an accommodating lensdevice 32″″ is shown having an optic portion 34″″ and haptic elements40″″ wherein the thickness of the haptic elements 40″″ is greater thanthe thickness of the optic portion 34″″ Alternatively, the modulus ofelasticity of the material of haptic elements 40″″ may be greater thanthe modulus of elasticity of the material of the optic portion 34″″. Inthis configuration, when tension is applied radially, as depicted by thearrows 901 of FIG. 9A, the radius of curvature of the optic portion 34″″increases. When the tension is released, the optic portion 34″″ revertsback to its natural state with a smaller radius of curvature as shown inFIG. 9B. Such operations provide for change in diopter of the opticportion 34″″ and accommodation of the lens device. By forming the opticportion 34″″ with a smaller thickness (or smaller modulus of elasticity)that the haptic elements 40″″, the response (e.g., change in diopter) ofthe optic portion 34″″ to the radial tension forces applied thereto ismaximized, which allows for a greater range of accommodation of the eye.The smaller thickness optic portion 34″″ may also allow for the scleralincision to be made smaller and thus provide for more effective healingof the eye post-operatively as noted above.

It was surprisingly found that the polyisobutylene-based material of theintraocular lens 32 as described herein has a high index of refractionranging from 1.52 to 1.54. This relatively high index of refractionprovides for improved magnification capabilities, and also allows thelens 23 to be thinner for a given magnification factor. Decreasing thethickness of the lens 23 is advantageous because it allows the scleralincision to be made smaller and thus provide for more effective healingof the eye post-operatively as noted above. It also provides forimproved response to ciliary muscle contraction and relaxation as notedabove.

It was also surprisingly found that the SIBS material of the intraocularlens 32 effectively blocks ultra-violet light. More particularly, thearomatic styrene groups of the polystyrene-polyisobutylene-polystyreneSIBS material are natural intrinsic filters of ultra-violet light. Thus,the exemplary SIBS material of the intraocular lens 32 mayadvantageously block ultra-violet light without the need for potentiallytoxic additives.

The polymeric intraocular lens 32 of the present invention can be loadedwith therapeutic drugs that release over time and interfere with theability of the epithelial cells of the eye to migrate and reproduce, andthereby protect against PCO. It is expected that the amount of drugrequired for this therapy will be in the picogram to microgram range.The therapeutic drugs loaded into the intraocular lens can includecytostatic agents (i.e., antiproliferation agents that prevent or delaycell division, for example, by inhibiting replication of DNA or byinhibiting spindle fiber formation, and/or inhibit the migration ofcells into the posterior space).

Representative examples of cytostatic agents include the following:

-   -   modified toxins;    -   methotrexate;    -   adriamycin    -   radionuclides (e.g., such as disclosed in U.S. Pat. No.        4,897,255, herein incorporated by reference in it entirety);    -   protein kinase inhibitors, including staurosporin (which is a        protein kinase C inhibitor) as well as a diindoloalkaloids and        stimulators of the production or activation of TGF-beta,        including tamoxifen and derivatives of functional equivalents        (e.g., plasmin, heparin, compounds capable of reducing the level        or inactivating the lipoprotein Lp(a) or the glycoprotein        apolipoprotein(a) thereof)    -   nitric oxide releasing compounds (e.g., nitroglycerin) or        analogs or functional equivalents thereof;    -   paclitaxel or analogs or functional equivalents thereof (e.g.,        taxotere), for example an agent based on Taxol® (whose active        ingredient is paclitaxel);    -   inhibitors of specific enzymes (such as the nuclear enzyme DNA        topoisomerase II and DAN polymerase, RNA polyermase, adenl        guanyl cyclase);    -   superoxide dismutase inhibitors;    -   terminal deoxynucleotidyl-transferas;    -   reverse transcriptase;    -   antisense oligonucleotides that suppress smooth muscle cell        proliferation;    -   angiogenesis inhibitors (e.g., endostatin, angiostatin and        squalamine);    -   rapamycin;    -   cerivastatin; and    -   flavopiridol and suramin and the like.

Other examples of cytostatic agents include the following:

-   -   peptidic or mimetic inhibitors (i.e., antagonists, agonists, or        competitive or non-competitive inhibitors) of cellular factors        that may (e.g., ion the presence of extracellular matrix)        trigger proliferation of cells or pericytes (e.g., cytokines        (for example, interleukins such as IL-1), growth factors (for        example, PDGF, TGF-alpha or -beta, tumor necrosis factor, smooth        muscle- and endothelioal-derived growth factors such as        endothelin or FGF), homing receptors (for example, for platelets        or leukocytes), and extracellular matrix receptors (for example,        integrins).

Representative examples of useful therapeutic agents in the category ofagents that address cell proliferation include:

-   -   subfragments of heparin;    -   triazolopyrimidine (for example, trapidil, which is a PDGF        antagonist);    -   lovastatin; and    -   prostaglandins E1 or I2.

Representative examples of therapeutic agents that inhibit migration ofcells into the posterior space include the following:

-   -   agents derived from phenylalanine (for example cytochalasins),        tryptophan (for example (chetogobosins), or luecine (for        example, asphalasins, resulting in a benzyl, indol-3-yl methyl        or isobutyl group, respectively, at position C-3 of a        substituted perhydroisoindole-1-one moiety.

Several of the above and numerous additional therapeutic agentsappropriate for the practice of the present invention are disclosed inU.S. Pat. Nos. 5,733,925 and 6,545,097, both of which are hereinincorporated by reference in their entirety.

If desired, a therapeutic agent of interest can be provided at the sametime as the copolymer, for example, by adding it to a copolymer meltduring thermoplastic processing or by adding it to a copolymer solutionduring solvent-based processing. The therapeutic agent can be added tothe optics portion or to the haptic elements or to both the opticsportion and the haptic elements of the lens device.

Alternatively, a therapeutic agent can be provided after formation ofthe device or device portion. As an example of these embodiments, thetherapeutic agent can be dissolved in a solvent that is compatible withboth the copolymer and the therapeutic agent. Preferably, the lenscopolymer is at most only slightly soluble in the solvent. Subsequently,the solution is contacted with the device or device portion such thatthe therapeutic agent is loaded (e.g., by leaching/diffusion) into thecopolymer. For this purpose, the device or device portion can beimmersed or dipped into the solution, the solution can be applied to thedevice or component, for example, by spraying, printing dip coating,immersing in a fluidized bed and so forth. The device or component cansubsequently be dried, with the therapeutic agent remaining therein.

In another alternative, the therapeutic agent may be provided within amatrix comprising the copolymer of the intraocular lens. The therapeuticagent can also be covalently bonded, hydrogen bonded, orelectrostatically bound to the copolymer. As specific examples, nitricoxide releasing functional groups such as S-nitroso-thiols can beprovided in connection with the copolymer, or the copolymer can beprovided with charged functional groups to attach therapeutic groupswith oppositely charged functionalities.

In yet another alternative embodiment, the therapeutic agent can beprecipitated onto the surface of a lens device or lens device portion.This surface can be subsequently covered with a coating of copolymer(with or without additional therapeutic agent) as described above.

Hence, when it is stated herein that the copolymer is “loaded” withtherapeutic agent, it is meant that the therapeutic agent is associatedwith the copolymer in a fashion like those discussed above or in arelated fashion.

In some instances a binder may be useful for adhesion to a substrate.Examples of materials appropriate for binders in connection with thepresent invention include silanes, titanates, isocyanates, carboxyls,amides, amines, acrylates hydroxyls, and epoxides, including specificpolymers such as EVA, polyisobutylene, natural rubbers, polyurethanes,siloxane coupling agents, ethylene and propylene oxides.

It also may be useful to coat the copolymer of the lens (which may ormay not contain a therapeutic agent) with a layer with an additionalpolymer layer (which may or may not contain a therapeutic agent). Thislayer may serve, for example, as a boundary layer to retard diffusion ofthe therapeutic agent and prevent a burst phenomenon whereby much of theagent is released immediately upon exposure of the lens device or deviceportion to the implant site. The material constituting the coating, orboundary layer, may or may not be the same copolymer as the loadedcopolymer.

For example, the barrier layer may also be a polymer or small moleculefrom the following classes: polycarboxylic acids, including polyacrylicacid; cellulosic polymers, including cellulose acetate and cellulosenitrate; gelatin; polyvinylpyrrolidone; cross-linkedpolyvinylpyrrolidone; polyanhydrides including maleic anhydridepolymers; polyamides; polyvinyl alcohols; copolymers of vinyl monomerssuch as EVA (ethylene-vinyl acetate copolymer); polyvinyl ethers;polyvinyl aromatics; polyethylene oxides; glycosaminoglycans;polysaccharides; polyesters including polyethylene terephthalate;polyacrylamides; polyethers; polyether sulfone; polycarbonate;polyalkylenes including polypropylene, polyethylene and high molecularweight polyethylene; halogenated polyalkylenes includingpolytetrafluoroethylene; polyurethanes; polyorthoesters; polypeptides,including proteins; silicones; siloxane polymers; polylactic acid;polyglycolic acid; polycaprolactone; polyhydroxybutyrate valerate andblends and copolymers thereof; coatings from polymer dispersions such aspolyurethane dispersions (BAYHDROL.RTM., etc.); fibrin; collagen andderivatives thereof; polysaccharides such as celluloses, starches,dextrans, alginates and derivatives; and hyaluronic acid. Copolymers andmixtures of the above are also contemplated.

It is also possible to form the lens device (or lens device portion)with blends by adding one or more of the above or other polymers to ablock copolymer. Examples include the following:

-   -   blends can be formed with homopolymers that are miscible with        one of the block copolymer phases. For example, polyphenylene        oxide is miscible with the styrene blocks of        polystyrene-polyisobutylene-polystyrene copolymer. This should        increase the strength of a molded part or coating made from        polystyrene-polyisobutylene-polystyrene copolymer and        polyphenylene oxide.    -   blends can be made with added polymers or other copolymers that        are not completely miscible with the blocks of the block        copolymer. The added polymer or copolymer may be advantageous,        for example, in that it is compatible with another therapeutic        agent, or it may alter the release rate of the therapeutic agent        from the block copolymer (e.g.,        polystyrene-polyisobutylene-polystyrene copolymer).    -   blends can be made with a component such as sugar (see list        above) that can be leached from the device or device portion,        rendering the device or device component more porous and        controlling the release rate through the porous structure.

The release rate of therapeutic agent from the therapeutic-agent-loadedblock copolymers of the present invention can be varied in a number ofways. Examples include:

-   -   varying the molecular weight of the block copolymers;    -   varying the specific constituents selected for the elastomeric        and thermoplastic portions of the block copolymers and the        relative amounts of these constituents;    -   varying the type and relative amounts of solvents used in        processing the block copolymers;    -   varying the porosity of the block copolymers;    -   providing a boundary layer over the block copolymer; and    -   blending the block copolymer with other polymers or copolymers.

Moreover, although it is seemingly desirable to provide control over therelease of the therapeutic agent (e.g., as a fast release (hours) or asa slow release (weeks)), it may not be necessary to control the releaseof the therapeutic agent. In such embodiments, one or more of thetherapeutic drug agents described herein (e.g., an antiproliferativeagent derived from paclitaxyl) may be injected into the lens capsule atthe time of surgery. In this case, the agent “sterilizes” the tissuecells that cause PCO within the short time it exists in the eye, and itcan be delivered neat (without a carrier) at the time of surgery.

For ocular applications, it is desirable that the material of at leastthe optic of the ocular lens device maintain in vivo transparency forsubstantial periods of time. As used herein, “in vivo transparency” or“transparent” shall mean that the material transmits at least 80% of thelight incident thereon in the visible range (e.g., between 400 and 700nm of the electromagnetic spectrum). It was found that a film of SIBSmaterial formed by traditional thermal processing techniques (e.g.,injection molding, compression molding, or extrusion at temperatures ator near the melting point of the SIBS material and then slow cooled tocure the polymer) is transparent in air; however, the film begins tocloud and become opaque with time when equilibrated in water, saline orother aqueous bodily fluids (collectively referred to below as “water”).Further, the extent of such clouding increases as the water is heated.At temperatures near the boiling point of water, the SIBS film becomestotally white-opaque and can absorb as much as 10% of its weight inwater. Considering that the SIBS material is comprised ofpolyisobutylene and polystyrene, which are both hydrophobic material,this result is surprising.

In accord with the present invention, the polyisobutylene-based materialof at least the optic of the ocular lens devices described herein isadapted to maintain in vivo transparency for substantial periods oftime. Generally, this is accomplished by satisfying the following twosteps: 1) washing remnant salts and other unwanted chemicals from thepolyisobutylene-based material; and 2) processing the washedpolyisobutylene-based material at a controlled temperature(s) and/or acontrolled processing time(s) to form the optic and possibly other partsof the ocular lens devices described herein. In one methodology, theoptic (and possibly other parts of the ocular lens device) is formed byprocessing the polyisobutylene-based polymer material at controlledtemperatures that are significantly less that the melting point of thepolyisobutylene-based polymer. In another methodology, the optic (andpossibly other parts of the ocular lens device) is formed by rapidlyheating the polyisobutylene-based polymer to a temperature at or nearits melting point. The resultant polymer melt is added to a mold thatforms the optic (and possibly other parts of the ocular lens device).The polymer and mold is quickly cooled back to room temperature forremoval of the optic. In addition, optical clarity additives may beadded to the polyisobutylene-based material to help in this regard;however, it is not always desirous to use these additives as they mayleach from the polymer and into the ocular environment and provoke anundesirable response.

The polyisobutylene-based material is typically synthesized in organicsolvent using a Lewis acid as an initiator. One such Lewis acid that ispreferred for this application is titanium tetrachloride. In order toquench the reaction, chemicals such as alcohols (methanol, for example)are added in excess to the reaction stoicheometry which immediatelyquenches the reaction by neutralizing titanium tetrachloride. Atcompletion of the reaction, titanium tetrachloride is converted intovarious salts of titanium, including titanium dioxide, titaniummethoxide, and the like. In addition, depending upon the reaction vesselused, various salts of titanium can form with materials inherent to thereaction vessel, especially if the vessel is comprised of stainlesssteel—these salts render the material black with time. Nevertheless, aconsequence of adding these reactant materials is that in order torender the material clean and highly transparent, these excess materialsand their byproducts must be removed from the polymer upon completion ofthe reaction.

These remnant salts and other unwanted chemicals are preferably washedfrom the polyisobutylene-based material by washing the polymer in aseparatory funnel with salt water, with pure water and with repeatedprecipitations in excess polar solvent (such as isopopanol, acetone,methanol, ethanol and the like). Other well-known washing procedures canalso be used. Note that if the material is not washed of salts, thesehygroscopic salts begin to draw in water when the material isequilibrated in water. Voids where the salts have been trapped arereadily viewed under scanning electron microscopy and these voids becomefilled with water as the salt is dissolved out. As water has arefractive index of approximately 1.33 and material has a refractiveindex of 1.53, the difference in refractive index is sufficient torender the polymer cloudy and at times totally opaque. If the materialis washed appropriately, these salts are removed and voids no longerexist.

In one methodology, the polyisobutylene-based material of the optic (andpossibly other parts of the ocular device described herein) is formedand molded at temperatures that are significantly less the melting pointof the material by casting the material from a solution. This isaccomplished by dissolving the polyisobutylene-based material in asolvent (such as hexanes, toluene, methylcyclohexane, cyclopentane, andthe like) and casting the resulting solution. Because casting fromsolution affords control over only one side of the lens, it is difficultto accurately form a lens with opposing optical surfaces utilizingcasting from solution alone. In these applications, casting fromsolution is preferably used to form a lens preform that is finished bycompression molding.

More particularly, the solution comprising the dissolvedpolyisobutylene-based material is cast into a preform mold therebyforming one or more lens preforms. The shape and dimensions of thepreform mold approach the geometry of the desired end product lens. Thelens preform(s) is (are) removed from preform mold and placed into acompression mold. The compression mold is pressed closed and heated fora predetermined duration at temperatures that are significantly lessthan the melting point of the material. The heating temperature andduration are selected such that the lens preform flows to its desiredfinal shape (with optically finished surfaces and the desired curvature)while the material maintains it's casting morphology. The end productlens is then removed from the compression mold. Once cooled, it has beenfound that the end product lens will maintain high transparency in theocular environment.

The SIBS material has a melting point between 200° C. and 250° C. Inthis case, the heating temperature utilized during the compressionmolding operations is preferably in the range between 100° C. and 120°C. for a duration between 10 to 90 minutes. At these parameters, theSIBS material maintains its casting morphology, that is the domainsegments remain intact and simply flow to fill the mold cavity.

The casting by solution operations that construct the preform preferablyutilize a centrifugal casting technique wherein a sheet of thepolyisobutylene-based material is cast within a rotating cylinder asshown in FIG. 10. The inside of the cylinder 1001 is lined with aTeflon® skin 1003. An array of evenly spaced indentations 1005 aremilled into the inner surface of the Teflon® skin (but not through theskin) preferably using a ball mill. The rotating cylinder 1001 issupported in an oven (not shown) that is operated at a heatingtemperature preferably in the range between 40° C. and 60° C. Thecylinder is rotated about is central axis preferably at a rotation speedof approximately 3000 RPM. As the cylinder 1001 is rotated, thepolyisobutylene-based solution (for example, polyisobutylene-basedmaterial dissolved in toluene solvent at a 10% wt/wt ratio) is injectedinto the cylinder 1001 as pictorially represented by the arrows 1007.The rotation of the cylinder 1001 produces centrifugal forces that forcethe solution against the inner surface of the skin 1003 and into theindentations 1005. The process can be repeated until the desired filmthickness is obtained. The film is then dried (typically requiringseveral hours drying time) and removed from the cylinder. The filmconsists of a ribbon of preform lenses (bumps) that are evenly locatedalong the ribbon. These preform lenses approach the geometry of thedesired end product lens, except that the surfaces are not opticallyfinished nor set to the desired curvature. The lens preforms are cut out(trephined) from the ribbon and placed into a compression mold thatforms the end product lens. Note that other polymeric castingtechniques, such as spin casting techniques, can also be used toconstruct the lens preforms at low temperatures relative to the meltingpoint of the polyisobutylene-based material.

The centrifugal casting of preform lenses together with compressionmolding finishing of the lenses advantageously provide a flexible,biocompatible polyisobutylene-based lens that maintains hightransparency in ocular fluid over time. Such operations are alsoadvantageous because they avoid the inefficiencies of the prior artmanufacturing methods. More specifically, the use of the Teflon® skin onthe inner surface of the centrifugal caster reduces the amount ofcleaning that is required between mold cycles. In addition, the lowtemperature compression molding operations helps reduce flash formation.These features provide for improved production cost efficiencies overthe prior art manufacturing methods.

In another methodology, the optic (and possibly other parts of theocular lens device) is formed by rapidly heating thepolyisobutylene-based polymer to a temperature at or near its meltingpoint. The resultant polymer melt is added to a mold that forms theoptic (and possibly other parts of the ocular lens device). The polymerand mold is quickly cooled back to room temperature for removal from themold. The polymer may be heated in the mold, or heated outside the moldand added to the mold in its melt state. For a polymer with 10 molepercent styrene content, the heating temperature range is 150° C. to200° C. and more preferably between 170° C. to 180° C. Preferably, thepolyisobutylene-based polymer is rapidly heated in a mold to thistemperature and the mold closed and pressurized to greater than 500 psiand then immediately rapidly cooled to room temperature. The rapidcooling can be accomplished by cooling coils, liquid nitrogen or thelike. The entire rapid heating-cooling cycle is preferably less thanthree (3) minutes, and more preferably less than one (1) minute suchthat the optic maintains in vivo transparency.

One can speculate that forming the ocular lens by traditional thermalprocessing of the polyisobutylene-based material without rapid heatingand cooling results in clouding in water due to the entrapment of watermolecules amongst the polyisobutylene chain segments. More particularly,when such material is heated to a temperature at or near its meltingtemperature and then allowed to slowly cool to room temperature, theglassy segments aggregate and segregate themselves from the softpolyisobutylene segments. This phase segmentation is known to occur inthese types of polymers as well as in other polymers, such aspolyurethane, and the like. It is further theorized that the watermolecules are trapped in the segments as when pure polyisobutylene isimmersed in water it clouds, whereas polystyrene does not cloud.Further, when the polymer is heated, there is more motility or vibrationin the chains, further entrapping water and hastening the clouding aswell as the extent of clouding. However, the polyisobutylene-basedmaterial cast from solution seems to segregate differently andexperiences minimal clouding in water.

Example 1

An ocular lens is constructed from a polyisobutylene-based material castfrom solution with a thickness of less than approximately 0.03 inches.The lens is placed in a water bath at 36° C. and maintains 95%-100%transparency in the visible spectrum over a period of two months.

Example 2

An ocular lens is constructed from a polyisobutylene-based material castfrom solution with a thickness of approximately 0.04 inches. The lens isplaced in a water bath at 36° C. and a slight amount of clouding isobserved by the naked eye after two days. Thereafter, lens maintains atransparency of 85%-95% in the visible spectrum over a period of twomonths.

Example 3

An ocular lens is molded from polyisobutylene-based material inconjunction with rapid heating and cooling of the material with athickness of less than approximately 0.03 inches. The lens is placed ina water bath at 36° C. and a slight amount of clouding is observed bythe naked eye after two days. Thereafter, lens maintains a transparencyof 85%-95% in the visible spectrum over a period of two months.

Optical clarity additives, such as mineral oil, paraffinic oil,naphthalic oil and small chains of polyisobutylene, and the like, can beadded to the polyisobutylene to help fill the voids between thepolyisobutylene strands that would otherwise trap water. Preferably,such additives are added to the polyisobutylene polymer at a ratiobetween 1% to 3% wt/wt. These optical clarity additives also helpmaintain the lenses highly transparent in both air and water; however,these additives are generally not desirable for implantationapplications as they may leach from the polyisobutylene polymer into theocular environment and provoke an undesirable response.

As noted above, the polyisobutylene-based material used in connectionwith the present invention is endowed with good biocompatibility. Thebiocompatibility of a polystyrene-polyisobutylene-polystyrene SIBScopolymer for the illustrative intraocular lens described herein isdemonstrated below in connection with the following non-limitingexample.

Example 4

Materials and Methods: SIBS material having a triblock polymer backbonecomprising polystyrene-polyisobutylene-polystyrene of mole percentstyrene content 9.8%, 21.5% and 23.4%, respectively, were synthesized byliving end carbocationic polymerization techniques. Also synthesized wasa control material made from medical grade polydimethylsiloxane (PDMS,RI=1.41). Both the SIBS material and the PDMS material were compressionmolded at 160° C. into flat disks, 3 mm and 6 mm diameter, all being 300μm thick. The disks were implanted in four groups of two New ZealandWhite rabbits using conventional surgical techniques. Maxitrol topicalointment was given for three days. No medications were given thereafter.Full ophthalmic examinations were performed weekly using a slit-lampbiomicroscope. Two animals with an endocapsular implant (intraocularlens) were followed until the eighth week and six animals withintracorneal and subtenon implants were followed until the twelfth weekbefore euthanasia for histology.

Results: No inflammation, infection, toxic reaction and implantmigration were observed. The cornea, sclera, iris, ciliary body,choroids, vitreous and retina remained normal in all animals. Noneovascularization or fibrosis could be detected around any SIBS disksimplanted intracorneally. Subtenon PDMS control implants elicited amoderate neovascularization reaction whereas the SIBS samples did not.Encapsulation was approximately 200 μm for PDMS and was well organizedand consistent around the sample. In addition, gross histology showedneovascularization (an ingrowth of capillaries) radiating from thesample. The histology for the SIBS samples routinely demonstrated aloose unorganized fibrous network with variable thickness ranging from 0to 100 μm around the sample with no signs of neovascularization.Scanning Electron Microscopy of the explanted SIBS discs showed no signsof biodegradation.

Conclusion: SIBS material is intraorbitally and intraocularlybiocompatible and does not encapsulate in the eye, and thus is suitablefor use in intraocular implant devices.

There have been described and illustrated herein several embodiments ofintraocular lens and surgical methods associated therewith. Whileparticular embodiments of the invention have been described, it is notintended that the invention be limited thereto, as it is intended thatthe invention be as broad in scope as the art will allow and that thespecification be read likewise. For example, it will be recognized thatadaptations may be made of the lens structures described herein. Moreparticularly, in the event that optic portion of the lens employs one ormore square edges, such edges introduce facets that can cause glare fromperipheral light sources. Such glare can be eliminated by frosting theedge of the optic. Alternatively, the shape and configuration of theoptic of the lens may be varied. For example, the optic may be realizedby first and second lens elements that are designed to be held in placealong the optical axis of the eye. The first lens element, which islocated posteriorly relative to the second lens, preferably has anegative power while the second lens element has a positive power. Apolymeric gel (for example, one formed of the in vivo SIBS materialdescribed herein) may be disposed between the two lens elements. One ormore of the therapeutic drug agents described herein (e.g., anantiproliferative agent derived from paclitaxyl) may be added to thepolymeric gel to inhibit PCO. In yet other embodiments, one or more ofthe therapeutic drug agents described herein (e.g., an antiproliferativeagent derived from paclitaxyl) may be associated with an ancillarydevice implanted in vivo in the eye, such as a lens tensioning device, asmall patch reservoir, or as a microcapsule. In another example, thelens devices described herein can be placed in the anterior chamber, inthe posterior chamber, or in the vitreous chamber. In yet anotherexample, the lens described herein can be used in conjunction with thenatural crystalline lens (e.g., the natural crystalline lens is notremoved) for eyes that suffer from severe refractive errors, or can alsobe used as a lens for corneal replacement, or for contact lens devices.

Moreover, while particular methods of manufacture have been disclosed,it will be understood that other manufacturing methods can be used. Forexample, because the copolymer materials described herein have athermoplastic character, a variety of standard thermoplastic processingtechniques can be used to for the devices described herein. Suchtechniques include compression molding, injection molding, blow molding,spinning, vacuum forming and calendering, and extrusion into tubes andthe like. Such devices can also be made using solvent-based techniquesinvolving solvent casting, spin coating, solvent spraying, dipping,fiber forming, ink jet techniques and the like.

It is also contemplated that the optically transparentpolyisobutylene-based material described herein (and methods offabricating such material) can be utilized into other medical implantapplications.

It will therefore be appreciated by those skilled in the art that yetother modifications could be made to the provided invention withoutdeviating from its spirit and scope as claimed.

1-54. (canceled)
 55. An ocular lens device for use in an ocularenvironment comprising: a deformable refractive optics structure that isconfigurable into an arrangement where the refractive optics structureis folded or rolled upon itself, said refractive optics structure havinga radius of curvature that varies according to accommodating forcesapplied by the ciliary muscles of the ocular environment.
 56. An ocularlens device according to claim 55, wherein: said refractive opticsstructure is foldable such that said device can be introduced through asmall scleral incision.
 57. An ocular lens device according to claim 57,wherein: the small sclera incision comprises a slit having a length of 2mm or less.
 58. An ocular lens device according to claim 55, wherein:said refractive optics structure is realized from apolyisobutylene-based polymer that is non-reactive in the ocularenvironment.
 59. An ocular lens device according to claim 58, wherein:said polyisobutylene-based polymer includes a glassy segment.
 60. Anocular lens device according to claim 58, wherein: saidpolyisobutylene-based polymer is processed to remove salts therefrom.61. An ocular lens device according to claim 58, wherein: saidpolyisobutylene-based polymer does not contain any cleavable group whichwill release in the presence of ocular fluid.
 62. An ocular lens deviceaccording to claim 59, wherein: said polyisobutylene-based polymercomprises a vinyl aromatic polymer.
 63. An ocular lens device accordingto claim 62, wherein: said vinyl aromatic polymer is selected from thegroup consisting of polystyrene, and α-methylstyrene.
 64. An ocular lensdevice according to claim 59, wherein: said polyisobutylene-basedpolymer comprises a methacrylate polymer.
 65. An ocular lens deviceaccording to claim 64, wherein: said methacrylate polymer is selectedfrom the group of a methylmethacrylate polymer, a ethylmethacrylatepolymer, and a hydroxymethacrylate polymer.
 66. An ocular lens deviceaccording to claim 55, wherein: said refractive optics structure isrealized from a material having a general block structure with a centralelastomeric polyolefinic block and thermoplastic end blocks.
 67. Anocular lens device according to claim 66, wherein: said materialcomprises a triblock polymer backbone comprisingPoly(styrene-block-isobutylene-block-styrene).
 68. An ocular lens deviceaccording to claim 66, wherein: said material has a general blockstructure selected from the group consisting of: a) BAB or ABA, b)B(AB)_(n), or A(BA)_(n), and c) X-(AB)_(n), or X-(BA)_(n); where A is anelastomeric polyolefinic block, B is a thermoplastic block, n is apositive whole number and X is a starting seed molecule.
 69. An ocularlens device according to claim 68, wherein: said material comprises acopolymer selected from the group consisting of a star-shaped blockcopolymer and multi-dendrite-shaped block copolymer.
 70. An ocular lensdevice according to claim 55, further comprising: an optic portion andat least one haptic element that are adapted to rest within a capsularbag formed by a surgical procedure, wherein said at least one hapticelement supports said optic portion.
 71. An ocular lens device accordingto claim 70, wherein: said at least one haptic element comprises anannular surface that surrounds and extends radially outward from saidoptic portion.
 72. An ocular lens device according to claim 71, wherein:said optic region is configured to be substantially disposed along aplane that is perpendicular to the optical axis of the ocularenvironment, and said annular surface projects radially outward fromsaid optic portion at an angle relative to said plane, said anglebetween 0 and 45 degrees.
 73. An ocular lens device according to claim72, wherein: said angle is between 10 and 20 degrees.
 74. An ocular lensdevice according to claim 73, wherein: said angle is 15 degrees.
 75. Anocular lens device according to claim 70, wherein: said optic portionhas a front convex surface and a flat back surface.
 76. An ocular lensdevice according to claim 70, wherein: said optic portion has a wall inits periphery which is thicker than the minimum thickness of said opticportion.
 77. An ocular lens device according to claim 70, wherein: saidoptic portion has a stepped wall structure at its periphery.
 78. Anocular lens device according to claim 70, wherein: said optic portionand said at least one haptic element are formed from said material. 79.An ocular lens device according to claim 70, wherein: said optic portionis formed from said material, and said at least one haptic element isformed from a different material.
 80. An ocular lens device according toclaim 58, wherein: said polyisobutylene-based polymer blocksultra-violet light.
 81. An ocular lens device according to claim 58,wherein: said polyisobutylene-based polymer is loaded with at least onetherapeutic agent that interferes with proliferation of the epithelialcells of the eye.
 82. An ocular lens device according to claim 58,wherein: said refractive optics structure is formed and molded attemperatures that are significantly less that the melting point of thepolyisobutylene-based polymer.
 83. An ocular lens device according toclaim 58, wherein: said refractive optics structure is formed bycompression molding in conjunction with rapid heating to a temperatureat or near the melting point of the polyisobutylene-based polymer andrapid cooling.
 84. An ocular lens device according to claim 83, wherein:time duration encompassing the rapid heating and the rapid coolingdefines a heating-cooling cycle that is less than three minutes.
 85. Anocular lens device according to claim 84, wherein: said heat-coolingcycle is less than one minute.
 86. An ocular lens according to claim 83,wherein: the rapid heating and rapid cooling is applied to therefractive optics structure during compression molding with therefractive optics structure disposed within a compression mold.
 87. Anocular lens device according to claim 58, wherein: said refractiveoptics structure is formed by dissolving said polyisobutylene-basedpolymer in a solvent to form a solution and casting the solution.
 88. Anocular lens device according to claim 87, wherein: the casting of thesolution forms at least one lens preform, and said refractive opticsstructure is formed by compression molding of said at least one lenspreform.